SOX2 silencing in glioblastoma tumor-initiating cells causes stop of proliferation and loss of tumorigenicity.
Glioblastoma, the most aggressive cerebral tumor, is invariably lethal. Glioblastoma cells express several genes typical of normal neural stem cells. One of them, SOX2, is a master gene involved in sustaining self-renewal of several stem cells, in particular neural stem cells. To investigate its role in the aberrant growth of glioblastoma, we silenced SOX2 in freshly derived glioblastoma tumor-initiating cells (TICs). Our results indicate that SOX2 silenced glioblastoma TICs, despite the many mutations they have accumulated, stop proliferating and lose tumorigenicity in immunodeficient mice. SOX2 is then also fundamental for maintenance of the self-renewal capacity of neural stem cells when they have acquired cancer properties. SOX2, or its immediate downstream effectors, would then be an ideal target for glioblastoma therapy.
Gangemi
Rosaria Maria Rita
RM
Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Griffero
Fabrizio
F
Marubbi
Daniela
D
Perera
Marzia
M
Capra
Maria Cristina
MC
Malatesta
Paolo
P
Ravetti
Gian Luigi
GL
Zona
Gian Luigi
GL
Daga
Antonio
A
Corte
Giorgio
G
D000328:Adult; D000818:Animals; D019070:Cell Lineage; D049109:Cell Proliferation; D002999:Clone Cells; D020868:Gene Silencing; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D035683:MicroRNAs / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology*; D010641:Phenotype; D055748:SOXB1 Transcription Factors / Q000235:genetics*; D014410:Tumor Stem Cell Assay
D019394:Ki-67 Antigen; D035683:MicroRNAs; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors